The invention, in some embodiments, relates to the field of ophthalmic surgery.
The eye comprises three main layers: an outer layer of tough, white, opaque, membrane known as the sclera; a middle layer known as the choroid, the front of which is the iris; and an inner layer, known as the retina, which lines the back two-thirds of the eye. The retina consists of two sublayers: the sensory retina, which contains photoreceptor cells (rods and cones) which convert light images into electrochemical signals and the retinal pigment epithelium (RPE). Cells of the RPE absorb excess light and transport oxygen, nutrients, and cellular waste between the photoreceptors and the choroid. The RPE is separated from the photoreceptor outer segments by the subretinal space.
The macula is an oval-shaped highly pigmented yellow spot near the center of the retina. Near the center of the macula is the fovea, a small pit that contains the largest concentration of cone cells in the eye and is responsible for central vision, and also contains the parafovea and perifovea.
Neuroretinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration (AMD), which involve death of cells in the RPE layer, are the major causes of blindness in the Western world. Such disorders are the consequence of various intrinsic and extrinsic factors and may result in the complete loss of visual function as a consequence of photoreceptor degeneration [Invest Opthalmol Vis Sci 48(1): 446-454 (2007)].
AMD is a progressive disease which primarily affects the macula. The risk for developing macular degeneration increases with age and is in excess of 30% by age 75. Other risk factors include a family history of the disease, cigarette smoking, excessive sunlight exposure, hypertension and cardiovascular disease. AMD is categorized as early AMD, dry AMD or wet AMD. The majority of AMD sufferers have early AMD, associated with minimal visual loss, which may progress to dry (atrophic) AMD or the more serious wet (exudative) AMD may develop.
In early AMD, the transport of nutrients and waste by the RPE slows down, so that waste accumulates under the retina forming yellowish deposits called drusen.
Dry macular degeneration is a slowly progressive condition characterized by the accumulation of drusen under the retina, with some visual loss. With increasing drusen accumulation, the overlying photoreceptors become damaged and atrophy.
In wet macular degeneration, new blood vessels grow underneath the retina in a process called choroidal neovascularization. These blood vessels may leak blood or fluid under the retina, causing the retinal surface to become uneven, so that portions of the visual field are distorted. As the condition progresses, blind spots may appear.
AMD affects approximately 8 million Americans, and its incidence is expected to double by 2020 [Transplantation 89(8): 911-919 (2010)]. Hence, AMD makes up a significant proportion of neurodegenerative diseases that severely impair activities of daily living.
Retinitis pigmentosa is a group of inherited diseases associated with abnormalities of the photoreceptors or the RPE, and characterized by progressive peripheral vision loss and night vision difficulties that can lead to central vision loss.
It has been suggested that cell-based therapy, wherein cells such as progenitor cells or stem cells, are engrafted into the subretinal space, may prove efficacious for several currently untreatable conditions involving the RPE layer, including retinitis pigmentosa, and AMD [Invest Opthalmol Vis Sci 50(7): 3425-3431 (2009)]. Cell transplantation into the human retina has the potential to restore lost vision and to provide treatment of advanced stages of retinal degeneration with significant RPE loss.
Subretinal injection is commonly used clinically for the delivery of therapeutic compositions to the subretinal space. An efficient delivery method is expected to achieve a uniform distribution of injected composition throughout the subretinal space including to the macula.
Known methods of subretinal delivery include those in which a sharp injection device, e.g., a syringe having a sharpened hollow needle, is used to penetrate the sclera from outside the eye to the subretinal space where the composition is injected. A major drawback of this method is that the composition remains localized in the subretinal space near the injection site and does not reach the macula.
Other methods which are intended to deliver compositions to the macula include inserting a thin flexible catheter from an incision site in the front sclera, through the subretinal space from the incision site until the distal end of the catheter is near the macula to deliver the composition near the macula. Disadvantages of such methods include the risk of severe detachment of the retina from the sclera caused by the catheter, and risk of damaging the retina during the procedure.
In another known method, an incision is made in the frontal part of the sclera and a sharp rigid cannula is inserted into an incision in the eye, across the eye, through the vitreous humor chamber to pierce the sensory retina across the incision site to enter the subretinal space near the macula where the composition is delivered. In addition to the fact that the injected compound remains localized in the subretinal space near the injection site, other drawbacks of this vitrectomy-like surgery include increased chance of cataract development, high ocular pressure and bleeding in the eye. Moreover, the need for repeated injections may require several incisions in the frontal part of the sclera.